Technological advances in the last few decades have brought the mammalian body in intimate contact with a variety of devices incorporating foreign materials which were not present in the evolution of their systems. Although many of these devices function as designed, a substantial number of them suffer from serious drawbacks. This appears to be particularly true when a device prepared from a foreign material is in contact with the blood of a mammal. All presently available materials which are in contact with the blood for significant periods of time induce deposition of blood cells and fibrin. This problem has hampered the practical development of artifical organs, extra-corporeal shunts, renal dialysis systems, catheters, heart-lung machines and the like. Solution of the problem is also important for in vitro systems such as blood collection and storage containers, for example.
Interaction of blood with the surface of a foreign material can result in two related but distinct processes. The first is a formation of a platelet thrombus which may lead to a second process, namely, coagulation, particularly in areas of slow blood flow. However, coagulation can occur in the absence of platelet interaction, particularly in in vitro systems.
The platelet thrombosis process is initiated by the adherence of blood platelets to the foreign surface with subsequent platelet-platelet interaction or aggregation leading to formation of a thrombus composed almost entirely of platelets. In areas of rapid blood flow, such as the cage of an artificial heart valve or in arterial grafts, the primary difficulty is platelet thrombosis and thromboembolism. Aggregated platelets release a factor which may stimulate a second process, blood coagulation, leading to formation of a fibrin blood clot. Clot formation is of major importance in areas of slow blood flow such as around the sewing ring of a valve or in venous circulation. Although platelet thrombi do not always result in clot formation, they can produce deleterious effects themselves. Since there is not a generic description covering both of these processes, a substance which inhibits platelet aggregation will hereinafter be referred to as "antithrombotic" and a substance which inhibits fibrin clot formation will hereinafter be referred to as "anticlotting".
Previously, researchers have attacked the problem of deposition of blood cells and fibrin on the surfaces of materials primarily by attempting to inhibit clot formation. The most common approach has been to coat the surface or impregnate the material with an anticoagulent, primarily heparin. Because there is no known method of directly binding heparin to materials, the heparin is bound to an intermediate chemical which is also bound to the particular material.
The binding of the intermediate to the material was done initially through adsorption. Since this surface gradually wore off the material, an ionic type of intermediate became employed more frequently. The lifetime of this coating was generally longer but it gradually wore off, as well. Recently, the intermediate compound has been covalently bound to the material. However, this covalent bonding is dependent upon a reactive group such as gamma propylamine in or interspersed within the material, or on radiation grafting.